Tag: ischaemic stroke

Categories : Neurodegenerative Diseases NeurologyTags :

Study Discovers a New Driver of Brain Haemorrhage Formation

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A recent study has revealed a new culprit in the formation of brain haemorrhages that does not involve injury to the blood vessels, as previously believed. In the first-of-its kind study, researchers led by the University of California, Irvine discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, offering deeper insights into how they occur and identifying potential new therapeutic targets for treatment and prevention.

The findings, published in the Journal of Neuroinflammation, describe how the team was able to watch the process by which red blood cells stall in the brain capillaries and then observe how the haemorrhage happens.

Cerebral microbleeds are associated with a variety of conditions that occur at higher rates in older adults, including hypertension, Alzheimer’s disease and ischaemic stroke.

“We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop,” said co-corresponding author Dr Mark Fisher, professor of neurology in UCI’s School of Medicine.

“Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral haemorrhages that occurs at the capillary level.”

The team exposed red blood cells to a chemical called tert-butyl hydroperoxide that caused oxidative stress; the cells were then marked with a fluorescent label and injected into mice.

Using two different methods, the researchers observed the red blood cells getting stuck in the brain capillaries and then being cleared out in a process called endothelial erythrophagocytosis.

As they moved out of the capillaries, microglia inflammatory cells engulfed the red blood cells, which led to the formation of a brain haemorrhage.

“It has always been assumed that in order for cerebral haemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development,” said co-corresponding author Xiangmin Xu, UCI professor of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping.

“We need to examine in detail the regulation of brain capillary clearance and also analyse how that process may be related to insufficient blood supply and ischaemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”

Source: University of California – Irvine

Categories : Cardiovascular DiseaseTags :

Can Taking Statins after an Intracerebral Haemorrhage Reduce the Risk of Another Stroke?

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Patients who have had an intracerebral haemorrhage who take cholesterol-lowering drugs called statins may have a lower risk of having another stroke, especially ischaemic stroke, compared to people who also had an intracerebral haemorrhage but were not taking statins, according to a new study published in Neurology, the medical journal of the American Academy of Neurology.

“Previous research has had mixed results on the risk of stroke in people who are taking statins and have already had a bleeding stroke, so we evaluated this further,” said study author David Gaist, MD, PhD, of the University of Southern Denmark in Odense and a member of the American Academy of Neurology. “We looked at whether use of statins after a bleeding stroke is associated with the risk of any additional stroke, including both those caused by bleeding and by blood clots. We found that those who used statins had a lower risk of stroke, notably ischaemic stroke, while there was no change in the risk of bleeding stroke.”

For the study, researchers looked at health records in Denmark and identified 15 151 people who had a first bleeding stroke.

People were followed from 30 days after their first bleeding stroke until the first occurrence of another stroke, death, or the end of follow-up, which on average lasted 3.3 years. Researchers used prescription data to determine information on statin use.

Researchers then compared 1959 people who had another stroke to 7400 people who did not have another stroke who were similar in age, sex and other factors. Of those who had another stroke, 757 people, or 39%, took statins compared to 3044 people, or 41%, of those who did not have a second stroke.

After adjusting for factors like hypertension, diabetes and alcohol use, statin use was associated with a 12% lower risk of another stroke.

Then they compared 1073 people who had an ischaemic stroke to 4,035 people who did not have another stroke. Of those who had an ischaemic stroke, 427 people, or 40%, took statins compared to 1687 people, or 42%, of those who did not have another stroke.

After adjusting for similar factors, statin use was associated with a 21% lower risk of an ischaemic stroke after the initial bleeding stroke.

They also compared 984 people who had another bleeding stroke to 3755 people who did not have another stroke. Of those who had a recurrent bleeding stroke, 385 people, or 39%, took statins compared to 1532 people, or 41%, of those who did not have another stroke.

After adjustments, researchers did not find a link between statin use and recurrent bleeding stroke.

“The results of our study are good news for people taking statins who have had a bleeding stroke,” Gaist added. “While we did find a lower risk of having another stroke, it is important to note that when looking at the data more closely, that lower risk was for ischaemic stroke. Still, we found no increased risk for bleeding stroke. More studies are needed to confirm our findings.”

A limitation of the study was that it only included the Danish population, which is primarily people of European ancestry, and may not be generalisable to people from other populations.

Source: American Academy of Neurology

Categories : Ageing Cardiovascular DiseaseTags :

Rethink Preventative Aspirin for Older Adults, Researchers Say

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Low-dose aspirin is used as primary prevention for ischaemic stroke, but its protective effect weighed against the increased risk of bleeding events is controversial. A new secondary analysis of daily aspirin in older people found that, in this population, aspirin failed to reduce the risk for ischaemic stroke but increased it for intracranial bleeding. The findings were presented in JAMA Network Open.

The researchers analysed data from the ASPREE randomised clinical trial, the first large-scale trial to study the risks and benefits of 100mg daily aspirin in an older population, where increased bleeding risk may alter the balance of risks and benefits of aspirin. This is particularly relevant to intracerebral events because intracranial haemorrhage is harder to treat than ischaemic events and more frequently fatal or disabling. With previous aspirin trials in mostly younger participants, excess intracerebral haemorrhagic events was seen, though usually few in number and non-significant.

Cloud et al. performed a secondary analysis of the ASPREE trial, which included 19 114 older adults, and found a statistically significant 38% increase in intracranial bleeding resulting from a combination of haemorrhagic stroke and other causes of intracerebral haemorrhage among individuals randomised to aspirin. The difference in incidence of ischaemic stroke was not statistically significant.

While aspirin did not cause a statistically significant reduction in ischaemic stroke (hazard ratio [HR], 0.89), there was a a statistically significant 38% increase in intracranial bleeding. Rates of intracranial bleeding from those assigned to aspirin (1.1%) were higher than placebo (0.8%). This came from an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin (0.6%) compared with placebo (0.4%). Haemorrhagic stroke was recorded in 0.5% of those assigned to aspirin compared with 0.4% for placebo.

Absolute numbers of haemorrhagic and non-haemorrhagic events were small. Among 1000 individuals taking 100mg/day of low-dose aspirin over five years, there were 2.5 fewer ischaemic strokes at the expense of 3.5 cases of intracranial haemorrhage, but not statistically significant. No difference would be expected for overall stroke incidence or stroke mortality, but haemorrhagic stroke was associated with a mortality rate of nearly a third, compared to 7.7% for ischaemic stroke. Major extracranial haemorrhage was driven by the increased risk of upper gastrointestinal bleeding with aspirin compared with placebo, as previously found (Hazard Ratio, 1.87).

The researchers concluded that “there was no statistically significant benefit from aspirin in preventing stroke or any conventional stroke etiological subtype. However, aspirin significantly increased the overall risk of intracranial bleeding.”

Categories : Cardiovascular Disease Surgeries & ProceduresTags :

Do not Automatically Bar Stroke Patients on Warfarin from EVT, Study Suggests

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Most ischaemic stroke patients taking the anticoagulant warfarin were no more likely than those not on the medication to experience a brain bleed when undergoing endovascular thrombectomy (EVT), UT Southwestern Medical Center researchers report in a new study. The findings, published in JAMA, could help doctors better gauge the risk of EVT, widening the pool of patients for this intervention.

“Although not very common, patients taking warfarin may still experience a stroke. In clinical practice, it’s very possible that some physicians may withhold an endovascular thrombectomy because patients have been treated with warfarin before their strokes. Our study could increase the number of patients for whom this lifesaving and function-saving surgery would be appropriate,” said study leader Ying Xian, MD, PhD, Associate Professor of Neurology at UT Southwestern.

EVT – a surgery that removes the clot by threading instruments through the blood vessels – is the most common treatment for acute ischaemic stroke. EVTs can sometimes cause potentially fatal symptomatic intracranial haemorrhage (sICH), Dr Xian explained. Although warfarin is a known risk factor for bleeding, it’s been unknown whether the risk of sICH following EVT is higher for stroke patients who have been on the blood thinner.

To help answer this question, Dr Xian worked with Eric Peterson, MD, MPH, Professor of Internal Medicine at UTSW, along with colleagues from other medical institutions across the country. Together, they gathered data on 32 715 stroke patients who underwent EVT within six hours of stroke symptom onset between 2015 and 2020. Data came from the American Heart Association’s Get with the Guidelines-Stroke registry – the world’s largest registry of stroke patients.

The researchers compared a variety of outcomes for the 3087 patients who took warfarin prior to stroke and the 29 628 patients who did not take any blood thinner. They evaluated whether patients experienced sICH within 36 hours of their EVT procedure, whether they had a serious systemic haemorrhage, or whether they had other complications that required additional medical intervention or an extended hospital stay. Researchers also tracked complications from additional therapies that reintroduced blood flow in the brain, in-hospital deaths, and discharges to hospice care.

After adjusting for differences inherent to patients taking or not taking warfarin, the researchers found no difference in overall risk of sICH or other adverse outcomes in patients in these two groups. However, patients with an international normalised ratio (INR) greater than 1.7 – a measure of clotting tendency of blood in patients taking warfarin – the risk of experiencing sICH increased by about 4%.

Whether this effect translates into worse outcomes for patients is unclear, Dr Peterson said. Except for higher risk of bleeding, these patients with INRs greater than 1.7 were no more likely than those not taking warfarin to die or have worse functional outcomes at discharge.

“Physicians must evaluate stroke patients on a case-by-case basis to determine whether EVT is appropriate, but our study suggests that taking warfarin alone should not necessarily be a limiting factor,” he added.

Drs Xian and Peterson said they are planning to study whether other anticoagulants frequently taken by patients at risk of stroke might increase the risk of sICH or other serious complications following EVT for ischaemic stroke.

Source: UT Southwestern Medical Center

Categories : Cardiovascular Disease GastrointestinalTags :

IBD Patients Have an Increased risk of Ischaemic Stroke

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Credit: American Heart Association

In a nationwide Swedish study of more than 85 000 patients with biopsy-confirmed inflammatory bowel disease (IBD), researchers saw an increased risk of stroke, especially ischaemic stroke, compared to the general population. The results are published in Neurology.

IBD is a chronic intestinal disease with a relapsing-remitting manner, including Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unclassified. Prior studies have suggested that IBD patients have a greater risk of thromboembolic events, but evidence for long-term risk of stroke remains scarce. A recent postmarketing safety study on tofacitinib, a new drug approved for IBD treatment, found an increased stroke risk.

The researchers, from Karolinska Institutet and Örebro University (Sweden), conducted a cohort study by linking a nationwide histopathology cohort (the ESPRESSO study) to national healthcare registers in Sweden to explore whether patients with a biopsy-confirmed IBD had an increased long-term risk of stroke compared to their IBD-free siblings or the general population.

During an average follow-up of 12 years, 3720 of IBD sufferers had a stroke (32.6/10 000 person years), compared with 15 599 of the IBD-free people (27.7/10 000 person-years). When accounting for other factors, such as heart disease, hypertension and obesity, they found that people with IBD were 13% more likely to have a stroke than those without IBD. The risk stayed elevated even 25 years after IBD diagnosis, equating to one additional stroke case per 93 IBD patients. The excess risk was mainly driven by ischaemic stroke rather than haemorrhagic stroke.

The risk for ischaemic stroke was significantly increased across all IBD subtypes (ie, CD, UC, and IBD-U). Sibling comparison analyses confirmed the main findings, suggesting the excess risk of stroke may be independent of familial factors.

Clinical implications

“Due to the excess risk of stroke in IBD patients, screening and management of traditional stroke risk factors in IBD patients could be more urgent to prevent fatal CVD complications”, says first author Jiangwei Sun, postdoc at the Department of Medical Epidemiology and Biostatistics.

“These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in IBD patients”, adds last author Jonas F Ludvigsson, professor at Karolinska Institutet and pediatrician at Örebro University Hospital.

Source: Karolinska Institutet

Categories : Cardiovascular Disease Exercise GenderTags :

Strenuous Jobs Increase Men’s Cardiovascular Risk, but Reduce Women’s

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Photo by K. Mitch Hodge on Unsplash

A long-term Danish study found that high physical activity at work was associated with higher risk of ischaemic heart disease (IHD) in men, but in women, this was associated with lower risk. The findings, published in the European Journal of Preventive Cardiology, highlight the importance of taking gender into account when considering the impact of high levels of occupational physical activity (OPA).

While previous studies have shown that physical activities in leisure time are protective against cardiovascular disease, high levels of OPA were shown to have no benefit – or even a detrimental effect.

The study followed up participants aged 30–61 years old after 34 years who took part in the Danish Monica 1 study in 1982–84. Participants, 1399 women and 1706 men, were actively employed, without prior IHD and who answered a question on OPA. The participants’ medical records were located in the Danish National Patient Registry and the researchers analysed the data, controlling for increasing numbers of factors such as age, then age and sex, and then age and sex plus factors such as smoking.

Compared to women doing sedentary work, women in all other OPA categories had a lower hazard ratio (HR) for IHD. Among men, the risk of IHD was 22% higher among those with light OPA, and 42% and 46% higher among those with moderate OPA with some lifting or strenuous work with heavy lifting, respectively, compared to men with sedentary OPA. Compared to women with sedentary work, HR for IHD was higher among men in all OPA categories, and a statistically significant interaction between OPA and sex was found.

Demanding or strenuous OPA seems to be a risk factor for IHD among men, whereas a higher level of OPA seems to protect from IHD among women. The researchers wrote that this underlines the importance of taking into account sex differences in studies of health effects of OPA. Future studies should investigate the underlying mechanisms for this difference, such as differences in exposure and physiology.

Categories : Cardiovascular Disease Lab Tests and ImagingTags :

Sex Differences in Brain Glycogen After a Stroke may Yield New Treatments

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Credit: American Heart Association

Although males and females are equally impacted by stroke, there are differences in recovery. Since oestrogen and progesterone have known neuroprotective effects, it is important to gauge their effects in stroke recovert. In a paper published in IBRO Neuroscience Reports, researchers have discovered differences between biomarkers such as glycogen levels in the brains of male and female mice.

“A stroke is caused by a loss of blood flow to brain cells. Without urgent intervention this may cause those cells to die because they constantly need energy and nutrients from the blood,” said Prof Nicole Sylvain, clinical research coordinator and lab manager at the University of Saskatchewan.

Sylvain and her colleagues are looking at treatments for post-stroke recovery that help supplement these energy losses. Using the Canadian Light Source (CLS) at the University of Saskatchewan (USask), the team was able to identify energy biomarkers in the brain, which could eventually inform clinicians about the effects of potential stroke treatments on brain recovery after a stroke.

The group’s recent study examined post-stroke differences between male and female mice, and found that female mice have higher amounts of glycogen in their brains. When the supply of glycogen is disrupted by stroke, the brain is severely impacted.

Most pre-clinical stroke research has been performed using male lab animals, with results usually generalised to both sexes. In clinical stoke cases, females have a higher incidence of ischaemic stroke and poorer outcomes, compared to males.

“We found that, for the most part, male data can be generalised for females, however, some of the metabolic markers we measured were actually different,” Sylvain said. “It’s really important to do the research on both sexes.”

It would be impossible for the team to detect the biomarkers without to the Mid-IR beamline.

“The only way to detect them in such an accurate way across the brain is with infrared imaging, so the CLS has been absolutely vital to our research.”

Source: University of Saskatchewan

Categories : Cardiovascular DiseaseTags :

Intensive Blood Pressure Reduction after Ischaemic Stroke Increases Disability

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Credit: American Heart Association

The largest ever randomised controlled trial of intensive blood pressure lowering after thrombectomy in ischaemic stroke patients found that it led to deterioration in surrounding brain tissue and higher rates of disability, compared to less intensive treatment.

The results of the ENCHANTED2/MT trial were presented in a late-breaking session at the World Stroke Congress and simultaneously published in The Lancet. The trial was stopped early due to the significance of the findings.

Professor Craig Anderson, Director of Global Brain Health at The George Institute for Global Health, said the rapid emergence of this effect suggested the more aggressive approach was compromising the return of blood flow to the affected area.

“Our study provides a strong indication that this increasingly common treatment strategy should now be avoided in clinical practice,” he said.

Endovascular thrombectomy is an increasingly used non-surgical treatment for ischaemic stroke, in which x-ray guided microcatheters are inserted into the blood clot to dissolve it.

“A potential downside of this now widely used and effective treatment is that the rapid return of blood supply to an area that has been deprived of oxygen for a while can cause tissue damage known as reperfusion injury,” said Professor Anderson.

“This has resulted in a shift in medical practice towards more intensive lowering of blood pressure after clot removal to try and minimise this damage, but without evidence to support the benefits versus potential harms.”

To this end, researchers recruited 816 adults with acute ischaemic stroke who had elevated blood pressure after clot removal from 44 centres in China between July 2020 and March 2022. They had an average age of 67 and just over a third were female.

Of these, 407 were assigned to more-intensive (target < 120mmHg) and 409 to the less-intensive (target 140–180mmHg) systolic blood pressure control, with the target to be achieved within one hour of entering the study and sustained for 72 hours.

Researchers looked at how well the patients in both groups recovered according to a standard measure of disability, ranging from 0–1 for a good outcome without or with symptoms but no disability, scores of 2–5 reflecting increasing disability levels, and 6 being death.

Patients in the more-intensively treated group had significantly worse scores on the scale compared to those allocated to those treated less intensively.

Compared to the less-intensive group, they had more early brain tissue deterioration and major disability at 90 days but there were no significant differences in brain bleeds, mortality, or serious adverse events.

Patients who had their blood pressure more intensively controlled also rated their quality of life as significantly worse due to limitations on their physical abilities resulting from their stroke.

Prof Anderson said that after scouring the medical literature the research team had been unable to find strong enough evidence to recommend the ideal target for blood pressure control after blood clot removal in patients with acute ischaemic stroke.

“While our study has now shown intensive blood pressure control to a systolic target of less than 120mmHg to be harmful, the optimal level of control is yet to be defined,” he said.

Source: George Institute for Global Health

Categories : Cardiovascular Disease GenderTags :

Sex Differences in Post-stroke Biomarkers

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Credit: American Heart Association

Although males and females are equally affected by stroke Since oestrogen and progesterone have known neuroprotective effects, it is important to compare the size, severity and biochemical composition of the brain tissue following stroke in female and male animal models. In a paper published in IBRO Neuroscience Reports, researchers have discovered that certain biomarkers were different in the brains of male and female mice.

Stroke neurosurgeon and research coordinator Prof Nicole Sylvain and her colleagues are looking at treatments for post-stroke recovery that help supplement these energy losses. Using the Canadian Light Source (CLS) at the University of Saskatchewan (USask), the team was able to identify energy biomarkers in the brain, which could eventually inform clinicians about the effects of potential stroke treatments on brain recovery after a stroke.

The group’s recent study examined post-stroke differences between male and female mice, and found that female mice have higher amounts of glycogen in their brains. Glycogen is a sugar-like substance that circulates in our blood and nourishes our cells. When the supply of glycogen is disrupted by stroke, the brain is severely impacted.

Most pre-clinical stroke research has been performed using male lab animals, with results usually generalised to both sexes. In clinical stoke cases, females have a higher incidence of ischaemic stroke and poorer outcomes, compared to males.

“We found that, for the most part, male data can be generalised for females, however, some of the metabolic markers we measured were actually different,” Sylvain said. “It’s really important to do the research on both sexes.”

It would be impossible for the team to detect the biomarkers without to the Mid-IR beamline.

“The only way to detect them in such an accurate way across the brain is with infrared imaging, so the CLS has been absolutely vital to our research.”

Source: University of Saskatchewan

Categories : Cardiovascular DiseaseTags :

Switch to Tenecteplase for Ischaemic Strokes Improves Outcomes and Lowers Costs

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Credit: American Heart Association

A newer, faster-administration clot-busting drug called tenecteplase outperforms the traditional treatment for ischaemic strokes in several key areas, including better health outcomes and lower costs, according to a new study published in the journal Stroke.

The 15-month study was led by a team of neurologists at Dell Medical School at The University of Texas at Austin.

“The Dell Med Neurology Stroke Program was one of the first in the United States to make this change,” said Steven Warach, MD, lead author of the study . “Based on even the earliest results from this study, other experts across the country were convinced and made the switch from alteplase to tenecteplase at their own stroke centres, including at Ascension hospitals nationwide.” 

The vast majority of strokes of the 800 000 strokes in the US (about 87%) each year are ischaemic.

Both tenecteplase and alteplase are federally approved for use in dissolving clots in blocked heart arteries. But the newer drug tenecteplase is also being used by clinicians, off-label, to treat ischaemic strokes, because clinical trials in stroke suggest that it may be at least as good as alteplase and it is easier to administer. Tenecteplase is administered by a single five- to 10-second intravenous injection. The researchers compared its performance with the standard drug for stroke, alteplase, which is injected over 60 minutes.

“When it comes to treating patients with a stroke, every second matters,” said Warach, who is also a professor of neurology at Dell Med. “The shorter preparation and injection time with tenecteplase not only eliminates a lot of dosing errors related to alteplase, but it’s also more efficient. We were able to deliver the clot-busting medicine more quickly after patients arrived in the emergency department, and for patients who needed to be transferred to another hospital for more advanced care after receiving the clot buster, we were able to initiate the transfer sooner in those treated with tenecteplase.”

For patients who come into the emergency department after a stroke, Warach’s study found that the “door-to-needle” time (from patients’ arrival to treatment) was on average six minutes quicker with tenecteplase. And for patients who also required a thrombectomy, the surgical removal of a blood clot causing the stroke, tenecteplase slashed to the time to transferring the patient to a thrombectomy-capable stroke centre by 25 minutes.

Researchers also saw improvements in clinical outcomes for patients given tenecteplase, including:

  • A 5% increase in patients who were able to walk independently at time of hospital discharge to home.
  • A 4% decrease in occurrences of bad events such as brain haemorrhages, discharge to hospice care or death.

The third major improvement: cost. The research team found that tenecteplase treatment cost the hospitals about US$ 2500 less than alteplase per patient.

Source: EurekAlert!